This project has established an improved humanized mouse model for the study of immune responses to HIV infection and vaccination. The model utilizes severely immunocompromised mice reconstituted with human thymic and liver tissue, which establishes human lymphocytic and monocytic populations susceptible to HIV infection. The mice support both intravenous and mucosal HIV infection and develop HIV-specific B and T cell immunity. We have been studying vaccine responses in the animals and are working on methods to improve vaccine efficacy and strengthen immune responses in humanized mice.